Method and system for delivering cardiac resynchronization therapy with variable atrio-ventricular delay

ABSTRACT

A pacing system computes optimal cardiac resynchronization pacing parameters using intrinsic conduction intervals. In various embodiments, values for atrio-ventricular delay intervals are each computed as a function of an intrinsic atrio-ventricular interval and a parameter reflective of an interventricular conduction delay. Examples of the parameter reflective of the interventricular conduction delay include QRS width and interval between right and left ventricular senses.

CLAIM OF PRIORITY

This application is a continuation of U.S. application Ser. No.12/622,602, filed Nov. 18, 2009, now issued as U.S. Pat. No. 8,121,685,which is a continuation of U.S. application Ser. No. 11/206,394, filedAug. 18, 2005, now issued as U.S. Pat. No. 7,630,764, which is acontinuation of application Ser. No. 10/744,944, filed on Dec. 22, 2003,now issued as U.S. Pat. No. 7,123,960, the specification of which isincorporated herein by reference in its entirety.

FIELD OF THE INVENTION

This invention pertains to methods and apparatus for treating cardiacdisease with electrical therapy.

BACKGROUND

Cardiac rhythm management devices are implantable devices that provideelectrical stimulation to selected chambers of the heart in order totreat disorders of cardiac rhythm. A pacemaker, for example, is acardiac rhythm management device that paces the heart with timed pacingpulses. The most common condition for which pacemakers are used is inthe treatment of bradycardia, where the ventricular rate is too slow.Atrio-ventricular conduction defects (i.e., AV block) that are permanentor intermittent and sick sinus syndrome represent the most common causesof bradycardia for which permanent pacing may be indicated. Iffunctioning properly, the pacemaker makes up for the heart's inabilityto pace itself at an appropriate rhythm in order to meet metabolicdemand by enforcing a minimum heart rate and/or artificially restoringAV conduction.

Pacing therapy can also be used in the treatment of heart failure, whichrefers to a clinical syndrome in which an abnormality of cardiacfunction causes a below normal cardiac output that can fall below alevel adequate to meet the metabolic demand of peripheral tissues. Whenuncompensated, it usually presents as congestive heart failure due tothe accompanying venous and pulmonary congestion. Heart failure can bedue to a variety of etiologies with ischemic heart disease being themost common. It has been shown that some heart failure patients sufferfrom intraventricular and/or interventricular conduction defects (e.g.,bundle branch blocks) such that their cardiac outputs can be increasedby improving the synchronization of ventricular contractions withelectrical stimulation. In order to treat these problems, implantablecardiac devices have been developed that provide appropriately timedelectrical stimulation to one or more heart chambers in an attempt toimprove the coordination of atrial and/or ventricular contractions,termed cardiac resynchronization therapy (CRT). Ventricularresynchronization is useful in treating heart failure because, althoughnot directly inotropic, resynchronization can result in a morecoordinated contraction of the ventricles with improved pumpingefficiency and increased cardiac output. Currently, a most common formof CRT applies stimulation pulses to both ventricles, eithersimultaneously or separated by a specified biventricular offsetinterval, and after a specified atrio-ventricular delay interval withrespect to the detection of an intrinsic atrial contraction and/or anatrial pace. Appropriate specification of these pacing parameters isnecessary in order to achieve optimum improvement in cardiac function,and it is this problem with which the present invention is primarilyconcerned.

SUMMARY

A pacing system computes optimal cardiac resynchronization pacingparameters using intrinsic conduction intervals. In various embodiments,values for atrio-ventricular delay intervals are each computed as afunction of an intrinsic atrio-ventricular interval and a parameterreflective of an interventricular conduction delay. Examples of theparameter reflective of the interventricular conduction delay includeQRS width and interval between right and left ventricular senses.

In one embodiment, a pacing system includes sensing/pacing channels anda controller. The sensing/pacing channels sense cardiac electricalactivity and deliver pacing pulses. The controller determines anatrio-ventricular delay (AVD) interval using at least an intrinsicatrio-ventricular interval measured following an atrial pace and aparameter reflective of an interventricular conduction delay. Using thefirst AVD interval, the controller controls the delivery of the pacingpulses in accordance with an AV sequential pacing mode.

In one embodiment, a pacing system includes means for determining atleast two AVD intervals and an implantable device that delivers acardiac resynchronization therapy using the two AVD intervals. One ofthe AVD intervals is for use in an atrio-ventricular sequential pacingmode and is determined using an intrinsic atrio-ventricular intervalmeasured between an atrial pace and a ventricular sense and a parameterreflective of an interventricular conduction delay. The other AVDinterval is for use in an atrial tracking mode and is determined usingan intrinsic atrio-ventricular interval measured between an atrial senseand another ventricular sense and the parameter reflective of theinterventricular conduction delay.

In one embodiment, a method for cardiac pacing is provided. An intrinsicatrio-ventricular interval is measured between an atrial pace and aventricular sense. An AVD interval is determined using the firstintrinsic atrio-ventricular interval and a parameter reflective of aninterventricular conduction delay. The AVD interval is used to controldelivery of pacing pulses in accordance with an AV sequential pacingmode.

In one embodiment, a method for cardiac pacing is provided. Twointrinsic atrio-ventricular intervals, one following an atrial pace andthe other following an atrial sense, are measured. A parameterreflective of an interventricular conduction delay is measured. An AVDinterval is used for pacing in an atrio-ventricular sequential pacingmode, and its value is computed using the intrinsic atrio-ventricularinterval following the atrial pace, the parameter reflective of theinterventricular conduction delay, and predetermined coefficients.Another AVD interval is used for pacing in an atrial tracking pacingmode, and its value is computed using the intrinsic atrio-ventricularinterval following the atrial sense, the parameter reflective of theinterventricular conduction delay, and predetermined coefficients.

This Summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and appended claims. Otheraspects of the invention will be apparent to persons skilled in the artupon reading and understanding the following detailed description andviewing the drawings that form a part thereof. The scope of the presentinvention is defined by the appended claims and their legal equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a system diagram of exemplary hardware components fordelivering cardiac resynchronization therapy.

FIG. 2 is a timing diagram showing the relationship between the RA-LAinterval and the programmed AVD interval.

FIG. 3 is an exemplary algorithm by which an implantable device may setthe AVD interval to different optimal values depending upon the atrialrate.

DETAILED DESCRIPTION

The present invention relates to a method or system for setting thepacing parameters and/or pacing configuration of a cardiac rhythmmanagement device for delivering resynchronization pacing to the leftventricle (LV) and/or the right ventricle (RV) in order to compensatefor ventricular conduction delays and improve the coordination ofventricular contractions. In accordance with the present invention,optimum pacing parameters may be computed based upon intrinsicconduction data derived from measurements of intra-cardiac conductiontimes using the sensing channels of an implanted device. Algorithms forcomputing and/or setting these pacing parameters may be implemented ineither the programming of an external programmer, in the programming ofthe implanted device itself, or as a manually implemented procedure(e.g., by using a printed table lookup to compute optimum parametersfrom intrinsic conduction data). In one embodiment, the externalprogrammer communicates with the implantable device over a telemetrylink and receives either raw electrogram data, markers corresponding toparticular sensed events, or measurements of the intervals betweenparticular sensed events as computed by the implantable device. Theexternal programmer may then compute optimal settings for pacingparameters which are either transmitted to the implantable device forimmediate reprogramming or presented to a clinician operating theexternal programmer as recommendations. Alternatively, the externalprogrammer may present the intrinsic conduction data to the clinicianwho then programs the implantable device in accordance with analgorithm. In another embodiment, the implantable device is programmedto automatically set certain pacing parameters in accordance withinformation gathered from its sensing channels.

As will be explained in more detail below, one aspect of the presentinvention involves the computation based upon intrinsic conduction dataof optimum atrio-ventricular delay (AVD) interval for deliveringventricular resynchronization therapy in an atrial tracking and/oratrio-ventricular sequential pacing mode to patients having some degreeof AV block or having an atrial conduction delay. Another aspect relatesto the optimal pacing configuration for delivering ventricularresynchronization therapy to patients having a right ventricularconduction deficit.

1. Exemplary Hardware Platform

The following is a description of exemplary hardware components used forpracticing the present invention. A block diagram of an implantablecardiac rhythm management device or pulse generator having multiplesensing and pacing channels is shown in FIG. 1. Pacing of the heart withan implanted device involves excitatory electrical stimulation of theheart by the delivery of pacing pulses to an electrode in electricalcontact with the myocardium. The device is usually implantedsubcutaneously on the patient's chest, and is connected to electrodes byleads threaded through the vessels of the upper venous system into theheart. An electrode can be incorporated into a sensing channel thatgenerates an electrogram signal representing cardiac electrical activityat the electrode site and/or incorporated into a pacing channel fordelivering pacing pulses to the site.

The controller of the device in FIG. 1 is made up of a microprocessor 10communicating with a memory 12 via a bidirectional data bus, where thememory 12 typically comprises a ROM (read-only memory) and, or a RAM(random-access memory). The controller could be implemented by othertypes of logic circuitry (e.g., discrete components or programmablelogic arrays) using a state machine type of design, but amicroprocessor-based system is preferable. As used herein, theprogramming of a controller should be taken to refer to either discretelogic circuitry configured to perform particular functions or to thecode executed by a microprocessor. The controller is capable ofoperating the pacemaker in a number of programmed modes where aprogrammed mode defines how pacing pulses are output in response tosensed events and expiration of time intervals. A telemetry interface 80is provided for communicating with an external programmer 300. Theexternal programmer is a computerized device with an associated displayand input means that can interrogate the pacemaker and receive storeddata as well as directly adjust the operating parameters of thepacemaker. As described below, in certain embodiments of a system forsetting pacing parameters, the external programmer may be utilized forcomputing optimal pacing parameters from data received from theimplantable device over the telemetry link which can then be setautomatically or presented to a clinician in the form ofrecommendations.

The embodiment shown in FIG. 1 has four sensing/pacing channels, where apacing channel is made up of a pulse generator connected to an electrodewhile a sensing channel is made up of the sense amplifier connected toan electrode. A MOS switching network 70 controlled by themicroprocessor is used to switch the electrodes from the input of asense amplifier to the output of a pulse generator. The switchingnetwork 70 also allows the sensing and pacing channels to be configuredby the controller with different combinations of the availableelectrodes. The channels may be configured as either atrial orventricular channels allowing the device to deliver conventionalventricular single-site pacing with or without atrial tracking,biventricular pacing, or multi-site pacing of a single chamber. In anexample configuration, a left atrial sensing/pacing channel includesring electrode 53 a and tip electrode 53 b of bipolar lead 53 c, senseamplifier 51, pulse generator 52, and a channel interface 50, and aright atrial sensing/pacing channel includes ring electrode 43 a and tipelectrode 43 b of bipolar lead 43 c, sense amplifier 41, pulse generator42, and a channel interface 40. A right ventricular sensing/pacingchannel includes ring electrode 23 a and tip electrode 23 b of bipolarlead 23 c, sense amplifier 21, pulse generator 22, and a channelinterface 20, and a left ventricular sensing/pacing channel includesring electrode 33 a and tip electrode 33 b of bipolar lead 33 c, senseamplifier 31, pulse generator 32, and a channel interface 30. Thechannel interfaces communicate bi-directionally with a port ofmicroprocessor 10 and include analog-to-digital converters fordigitizing sensing signal inputs from the sensing amplifiers, registersthat can be written to for adjusting the gain and threshold values ofthe sensing amplifiers, and registers for controlling the output ofpacing pulses and/or changing the pacing pulse amplitude. In thisembodiment, the device is equipped with bipolar leads that include twoelectrodes which are used for outputting a pacing pulse and/or sensingintrinsic activity. Other embodiments may employ unipolar leads withsingle electrodes for sensing and pacing. The switching network 70 mayconfigure a channel for unipolar sensing or pacing by referencing anelectrode of a unipolar or bipolar lead with the device housing or can60.

The controller 10 controls the overall operation of the device inaccordance with programmed instructions stored in memory. The controller10 interprets electrogram signals from the sensing channels and controlsthe delivery of paces in accordance with a pacing mode. An exertionlevel sensor 330 (e.g., an accelerometer, a minute ventilation sensor,or other sensor that measures a parameter related to metabolic demand)enables the controller to adapt the atrial and/or ventricular pacingrate in accordance with changes in the patient's physical activity,termed a rate-adaptive pacing mode. The sensing circuitry of the devicegenerates atrial and ventricular electrogram signals from the voltagessensed by the electrodes of a particular channel. An electrogram isanalogous to a surface EKG and indicates the time course and amplitudeof cardiac depolarization and repolarization that occurs during eitheran intrinsic or paced beat. When an electrogram signal in an atrial orventricular sensing channel exceeds a specified threshold, thecontroller detects an atrial or ventricular sense, respectively, whichpacing algorithms may employ to trigger or inhibit pacing.

2. Cardiac Resynchronization Pacing Therapy

Cardiac resynchronization therapy is most conveniently delivered inconjunction with a bradycardia pacing mode. Bradycardia pacing modesrefer to pacing algorithms used to pace the atria and/or ventricles in amanner that enforces a certain minimum heart rate. Because of the riskof inducing an arrhythmia with asynchronous pacing, most pacemakers fortreating bradycardia are programmed to operate synchronously in aso-called demand mode where sensed cardiac events occurring within adefined interval either trigger or inhibit a pacing pulse Inhibiteddemand pacing modes utilize escape intervals to control pacing inaccordance with sensed intrinsic activity. In an inhibited demand mode,a pacing pulse is delivered to a heart chamber during a cardiac cycleonly after expiration of a defined escape interval during which nointrinsic beat by the chamber is detected. For example, a ventricularescape interval for pacing the ventricles can be defined betweenventricular events, referred to as the cardiac cycle (CC) interval withits inverse being the lower rate limit or LRL. The CC interval isrestarted with each ventricular sense or pace. In atrial tracking and AVsequential pacing modes, another ventricular escape interval is definedbetween atrial and ventricular events, referred to as theatrio-ventricular pacing delay interval or AVD, where a ventricularpacing pulse is delivered upon expiration of the atrio-ventricularpacing delay interval if no ventricular sense occurs before. In anatrial tracking mode, the atrio-ventricular pacing delay interval istriggered by an atrial sense and stopped by a ventricular sense or pace.An atrial escape interval can also be defined for pacing the atriaeither alone or in addition to pacing the ventricles. In an AVsequential pacing mode, the atrio-ventricular delay interval istriggered by an atrial pace and stopped by a ventricular sense or pace.Atrial tracking and AV sequential pacing are commonly combined so thatan AVD starts with either an atrial pace or sense. When used in CRT, theAVD may be the same or different in the cases of atrial tracking and AVsequential pacing.

As described above, cardiac resynchronization therapy is pacingstimulation applied to one or more heart chambers in a manner thatcompensates for conduction delays. Ventricular resynchronization pacingis useful in treating heart failure in patients with interventricular orintraventricular conduction defects because, although not directlyinotropic, resynchronization results in a more coordinated contractionof the ventricles with improved pumping efficiency and increased cardiacoutput. Ventricular resynchronization can be achieved in certainpatients by pacing at a single unconventional site, such as the leftventricle instead of the right ventricle in patients with leftventricular conduction defects. Resynchronization pacing may alsoinvolve biventricular pacing with the paces to right and left ventriclesdelivered either simultaneously or sequentially, with the intervalbetween the paces termed the biventricular offset (BVO) interval (alsosometimes referred to as the LV offset (LVO) interval or VV delay). Theoffset interval may be zero in order to pace both ventriclessimultaneously, or non-zero in order to pace the left and rightventricles sequentially. As the term is used herein, a negative BVOrefers to pacing the left ventricle before the right, while a positiveBVO refers to pacing the right ventricle first. In an examplebiventricular resynchronization pacing mode, right atrial paces andsenses trigger an AVD interval which upon expiration results in a paceto one of the ventricles and which is stopped by a right ventricularsense. The contralateral ventricular pace is delivered at the specifiedBVO interval with respect to expiration of the AVD interval.

Cardiac resynchronization therapy is most commonly applied in thetreatment of patients with heart failure due to left ventriculardysfunction which is either caused by or contributed to by leftventricular conduction abnormalities. In such patients, the leftventricle or parts of the left ventricle contract later than normalduring systole which thereby impairs pumping efficiency. In order toresynchronize ventricular contractions in such patients, pacing therapyis applied such that the left ventricle or a portion of the leftventricle is pre-excited relative to when it would become depolarized inan intrinsic contraction. Optimal pre-excitation of the left ventriclein a given patient may be obtained with biventricular pacing or withleft ventricular-only pacing. Although not as common, some patients havea right ventricular conduction deficit such as right bundle branch blockand require pre-excitation of the right ventricle in order achievesynchronization of their ventricular contractions.

3. Optimal Adjustment of Pre-Excitation Timing Parameters

Once a particular resynchronization pacing configuration and mode isselected for a patient, pacing parameters affecting the manner andextent to which pre-excitation is applied must be specified. For optimumhemodynamic performance, it is desirable to deliver ventricular pacing,whether for resynchronization pacing or conventional bradycardia pacing,in an atrial tracking and/or AV sequential pacing mode in order tomaintain the function of the atria in pre-loading the ventricles(sometimes referred to atrio-ventricular synchrony). Since the objectiveof CRT is to improve a patient's cardiac pumping function, it istherefore normally delivered in an atrial-tracking and/or AV sequentialmode and requires specification of AVD and BVO intervals which, ideally,result in the ventricles being synchronized during systole after beingoptimally preloaded during atrial systole. That is, both optimalinterventricular synchrony and optimal atrio-ventricular synchrony areachieved. As the term is used herein for biventricular pacing, the AVDinterval refers to the interval between an atrial event (i.e., a pace orsense in one of the atria, usually the right atrium) and the firstventricular pace which pre-excites one of the ventricles. The AVDinterval may be the same or different depending upon whether it isinitiated by an atrial sense or pace (i.e., in atrial tracking and AVsequential pacing modes, respectively), The pacing instant for thenon-pre-excited ventricle is specified by the BVO interval so that it ispaced at an interval AVD+BVO after the atrial event. It should beappreciated that specifying AVD and BVO intervals is the same asspecifying a separate AVD interval for each ventricle, designated asAVDR for the right ventricle and AVDL for the left ventricle. Inpatients with intact and normally functioning AV conduction pathways,the non-pre-excited ventricle will be paced, if at all, close to thetime at which that ventricle is intrinsically activated in order toachieve optimal preloading. In patients with normal AV conduction, theoptimal AVD and BVO intervals are thus related to both the intrinsicatrio-ventricular interval and the amount of pre-excitation needed forone ventricle relative to the other (i.e., the extent of the ventricularconduction deficit).

In order to optimally specify the AVD and BVO parameters for aparticular patient, clinical hemodynamic testing may be performed afterimplantation where the parameters are varied as cardiac function isassessed. For example, a patient may be given resynchronizationstimulation while varying pre-excitation timing parameters in order todetermine the values of the parameters that result in maximum cardiacperformance, as determined by measuring a parameter reflective ofcardiac function such as maximum left ventricular pressure change(dP/dt), arterial pulse pressure, or measurements of cardiac output.Determining optimal pacing parameters for an individual patient byclinical hemodynamic testing, however, is difficult and costly. It wouldbe advantageous if such optimal pacing parameters could be determinedfrom measurements of intrinsic conduction parameters which reflect howexcitation is conducted within the patient's heart during intrinsicbeats. In the approach of the present invention, therefore, intrinsicconduction data is collected from a surface EKG or from the sensingchannels of the implantable cardiac resynchronization device and thenused to compute optimum values of resynchronization pacing parameters.

As noted above, the objective of CRT is to restore a normal ornear-normal conduction sequence to ventricular contractions by usingpacing pulses to compensate for interventricular and/or intraventricularconduction deficits. CRT is most commonly used to treat left ventriculardysfunction brought about by parts of the left ventricle contractinglater than normal during an intrinsic cardiac cycle. Biventricular (orleft ventricle-only) pacing accomplishes this by pre-exciting the leftventricle with a first pace delivered to the left ventricle followed bya pace to the right ventricle at the BVO interval (or intrinsicactivation of the right ventricle in the case of left ventricle-onlypacing). The left ventricle electrode excites the left ventricular freewall, while the right ventricle electrode excites the ventricularseptum. The desired situation is simultaneous contraction of the leftventricular free wall and septum (septum-free wall fusion). Whenclinical hemodynamic testing is performed on a population of subjectswith intact AV pathways to determine the optimum values of the AVD andBVO intervals, there is found to be a correlation between the optimumAVD and BVO intervals for a particular subject and that subject'smeasured conduction delay between the right and left ventricles duringan intrinsic beat. The optimum AVD interval and the intrinsicatrio-ventricular interval are also correlated from patient to patient.Therefore, the optimum AVD and BVO intervals for a particular patientmay be estimated from intrinsic conduction data in terms of specifiedcoefficients k_(n) as:BVO=k₁·Δ_(RL) +k ₂andAVD=k ₃AV_(R) +k ₃·Δ_(RL) +k ₄where Δ_(RL) is a measurement reflective of the interventricularconduction delay between the right and left ventricles such as theinterval between right and left ventricular senses or the QRS width on asurface ECG, and AV_(R) is the right intrinsic atrio-ventricularinterval measured as the interval between an atrial sense (or pace) anda right ventricular sense. It should be appreciated that these equationscan also be expressed in terms of separate AVD intervals for the rightand left ventricles, designated as AVDR and AVDL, respectively, andseparate measured intrinsic atrio-ventricular intervals for the rightand left ventricles, designated AV_(R) and AV_(L), respectively. Theintervals are thus related as:AV_(R)−AV_(L)=Δ_(RL) (if determined by right and left ventricularsenses)andAVDL−AVDR=BVOThe equations for computing optimal values of AVDR and AVDL are thus:AVDR=k ₅AV_(R) +k ₆AV_(L) +k ₇andAVDL=k ₈AV_(R) +k ₉AV_(L) +k ₁₀In certain implementations of the techniques described herein, separateintrinsic atrio-ventricular intervals are measured following an atrialsense and following an atrial pace which are then used to compute AVdelay intervals for pacing in atrial tracking and AV sequential modes,respectively. Also, unless otherwise specified, the term biventricularpacing should be taken to include left ventricle-only pacing. If thecomputed optimal BVO interval is a large negative value which is longerthan the right intrinsic atrio-ventricular interval, the right ventriclewill be activated intrinsically anyway so that the biventricular pacingis effectively left ventricle-only pacing.

In order to pre-derive the specified coefficients for later programminginto the system or for use by a clinician, clinical population data isobtained that relates particular values of the measured intrinsicconduction parameters to an optimum value of the pre-excitation timingparameter as determined by concurrent measurement of another parameterreflective of cardiac function (e.g., maximum dP/dt or minimum atrialrate). A linear regression analysis is then performed to derive valuesof the specified coefficients used in the formula for setting thepre-excitation timing parameter, the specified coefficients thus beingregression coefficients.

The techniques for setting resynchronization pacing parameters asdescribed above, as well as others to be described below, may beimplemented in a number of different ways. In one implementation, asystem for setting the pacing parameters includes an externalprogrammer. In an example embodiment, one or more intrinsic conductionparameters, as measured from electrogram signals generated by thesensing channels of an implantable cardiac resynchronization deviceduring intrinsic beats, are transmitted to the external programmer via awireless telemetry link. The measured intrinsic conduction parametersmay represent averages of values obtained during a specified number ofintrinsic beats. The external programmer then computes a pre-excitationtiming parameter such as the AVD or BVO in accordance with a formulathat equates an optimum value of the pre-excitation timing parameter toa linear sum of the measured intrinsic conduction parameters multipliedby specified coefficients. In an automated system, the externalprogrammer then automatically programs the implantable device with thecomputed optimum parameter values, while in a semi-automated system theexternal programmer presents the computed optimum values to a clinicianin the form of a recommendation. An automated system may also be made upof the implantable device alone which collects intrinsic conductiondata, computes the optimum parameter values, and then sets theparameters accordingly. In another embodiment, which may be referred toas a manual system, the external programmer presents the collectedintrinsic conduction data to a clinician who then programs theimplantable device with parameters computed from the intrinsicconduction data by, for example, using a printed lookup table andprocedure. Unless otherwise specified, references to a system forcomputing or setting pacing parameters throughout this document shouldbe taken to include any of the automated, semi-automated, or manualsystems just described.

4. Computation of Optimal Pacing Parameters Based Upon Atrial ConductionDelay

The above-described methods for computing optimal resynchronizationpacing parameters from intrinsic conduction data are based upon measuredintrinsic conduction data which include intrinsic atrio-ventricularintervals and/or interventricular conduction delays. Another measurableintrinsic conduction value which may be used in computing optimal pacingparameters is the conduction delay between the right and left atriaduring an intrinsic beat. One use of this technique is to computeoptimal resynchronization pacing parameters for patients with AV block.AV block refers to an impairment in the AV conduction pathways such thateither no intrinsic conduction from the atria to the ventricles occurs(complete or 3^(rd) degree AV block) or the intrinsic atrio-ventricularinterval is longer than normal. In patients with some degree of AVblock, the above techniques cannot be used to estimate the optimum AVDinterval for CRT because either no measured intrinsic atrio-ventricularinterval can be obtained or, if it can, it does not reflect optimumhemodynamics. In one aspect of the present invention, an optimum AVDinterval for pre-exciting the left ventricle in such patients mayinstead be computed from a linear function of the intrinsic delaybetween right atrial and left atrial activation, referred to as theRA-LA interval:AVD=k ₁₁(RA-LA)+k ₁₂where the AVD interval in this situation is the interval from an atrialevent to a left ventricular pace. The coefficients of the equation maybe obtained as before from a regression analysis of clinical populationdata. The technique may be implemented with the device in FIG. 1 usingthe right and left atrial sensing channels to measure the RA-LA intervalas the interval between right atrial pace or sense and a left atrialsense. After obtaining the optimum AVD interval, the BVO interval may beset to either a nominal value or computed from intrinsic conduction dataas described above.

The rationale for employing the RA-LA interval to compute an optimum AVDis as follows. When intrinsic depolarization is absent, ventricularsynchrony is optimized by delivering biventricular stimulation with orwithout an offset to result in septum-free wall fusion.Atrial-ventricular synchrony for the left atrium and left ventricle inthis situation is optimized when the onset of left ventricular pressurerise coincides with the peak of left atrial contraction. To achieveoptimal atrio-ventricular synchrony in the treatment of left ventriculardysfunction, stimulation to the left ventricle should therefore beapplied at a certain time ahead of peak contraction in the left atrium.FIG. 2 is a timing diagram which illustrates this point. During anintrinsic beat, a right atrial sense RA_(S) is followed by a leftventricular sense LA_(S) which is then followed by the peak of leftatrial contraction X. In a subsequent beat where the left ventricle ispaced at an optimal AVD interval with respect to a right atrial sense,the left ventricular pace LV_(P) results in the onset of leftventricular pressure rise Y coinciding with the peak of left atrialcontraction X. The optimum AVD interval is thus proportional to theinterval between the right atrial sense RA_(S) and the peak of leftatrial contraction X or its surrogate, the RA-LA interval between theright atrial sense RA_(S) and the left atrial sense LA_(S).

The RA-LA interval may also be used to compute optimal resynchronizationparameters in patients with normal AV conduction. For example, if it isdetermined that intrinsic left ventricular activation occurs later thanleft atrial activation by a specified threshold amount, it may bedesirable to compute the resynchronization pacing parameters based uponthe intrinsic atrio-ventricular interval, the interventricularconduction delay, and the RA-LA interval. Thus, the right ventricle maybe paced at an AVDR interval computed as described above as:AVDR=k ₅AV_(R) +k ₆AV_(L) +k ₇orAVDR=k ₃AV_(R) +k ₃·Δ_(RL) +k ₄The AVDL interval for pacing the left ventricle (or the BVO interval)may then be computed as a function of the RA-LA interval:AVDL=k ₁₃(RA-LA)+k ₁₄5. Variable AVD Interval

The optimal values of the AVD interval discussed above have beencomputed without regard to the atrial rate. For optimum hemodynamics,however, the AVD interval should vary with atrial rate in a mannersimilar to the way the intrinsic AV interval varies with atrial rate innormal individuals. Such physiological varying of the intrinsic AVinterval is due to neural and hormonal influences acting on the AV nodewhich cause the interval to shorten when sympathetic nervous activity ishigh and lengthen when parasympathetic nervous activity is high, whichfactors also act on the sino-atrial node to result in high and lowatrial rates, respectively. Since improvement in hemodynamics is theobjective of CRT, it would be desirable for a programmed AVD intervalused in delivering CRT to mimic the physiological varying of theintrinsic AV interval. Varying of the AVD interval would be especiallyuseful during high atrial rates caused by rate-adaptive pacing modes athigh exertion levels or atrial overdrive pacing algorithms.

The AVD interval may be varied by programming the implantable CRT devicewith a look-up table or function which maps particular atrial rates toparticular optimal AVD values. As the atrial rate changes, either due toatrial pacing or intrinsic atrial activity, the device may thendynamically compute the optimal AVD interval. For atrial rates which arenot in the table, a linear or non-linear interpolating function may beused. Such a table or function may be generated in various ways. One wayis during clinical hemodynamic testing where the AVD intervals whichresult in a maximized cardiac function parameter are determined fordifferent atrial rates. Examples of cardiac function parameters whichcould be used in this procedure include dP/dt, arterial pulse pressure(e.g., finger pulse pressure), and measurements of cardiac output.Determining multiple optimal AVD intervals in this manner, however, iseven more time-consuming and difficult than determining a single optimalnon-varying AVD interval using clinical hemodynamic testing.Accordingly, a system made up of an external programmer and animplantable device or the implantable device alone may use intrinsicconduction data collected by the implantable device's sensing channelsto compute optimal AVD intervals for a plurality of atrial rates.

In an exemplary embodiment, the system computes optimalatrio-ventricular delay (AVD) intervals to be used for deliveringcardiac resynchronization therapy to a particular patient by collectingintrinsic conduction data at different atrial rates. The atrial rate mayvary intrinsically or as a result of pacing during the data collection.Such data may be an intrinsic AV interval measured as the interval froman atrial sense or pace to a ventricular sense in the case of patientswith normal AV conduction, or the RA-LA interval measured as theinterval from a right atrial sense or pace to a left atrial sense in thecase of patients with or without normal AV conduction. The systemcomputes an optimal value of the AVD interval for delivering a leftventricular pace following an atrial event in an atrial tracking or AVsequential pacing mode as a linear function of the measured intrinsic AVinterval or the RA-LA interval in the same manner as described earlier.The computed optimal AVD interval value is associated with an atrialrate corresponding to the measured atrial rate which was present whenthe intrinsic AV interval or RA-LA interval was measured, with theoptimal AVD interval value and its associated atrial rate being storedin a table contained in the memory of the implantable device. Aftergenerating a table in this manner (e.g., after at least two such optimalAVD intervals have been stored in the table), the implantable device mayvary the AVD interval as the atrial rate changes (by, e.g.,rate-adaptive pacing of the atria or pacing the atria in accordance withan overdrive algorithm) by determining a present atrial rate and settingthe AVD interval to the optimum value stored in the table which isassociated with the present atrial rate. In one variation of theembodiment, the atrial rate associated with each optimal AVD valuestored in the table is a range defined by upper and lower limits. Theimplantable device then varies the AVD interval with the atrial rate byselecting an optimum AVD interval value from the table which isassociated with a range which encompasses the present atrial rate. Inanother variation, the implantable device varies the AVD interval ifthere is no associated atrial rate in the table corresponding to thepresent atrial rate by interpolating between two optimum AVD valuesstored in the table which have associated atrial rates above and belowthe present atrial rate using a linear or non-linear interpolationfunction. In still another variation, the implantable device isprogrammed to update the table if there is no associated atrial rate inthe table corresponding to the present atrial rate by measuring an RA-LAinterval or intrinsic AV interval, compute an optimal value for the AVDinterval as a linear function of the RA-LA interval or intrinsic AVinterval, and store the computed optimal value and an associated atrialrate corresponding to the present atrial rate in the table.

FIG. 3 illustrates an exemplary algorithm which may be implemented inthe programming of an implantable cardiac rhythm management device witha plurality of sensing/pacing channels for sensing cardiac electricalactivity and delivering pacing pulses to selected cardiac chambers and acontroller programmed to deliver biventricular pacing in accordance withan atrial tracking or AV sequential pacing mode and a programmableatrio-ventricular delay (AVD) interval. The controller is programmed todetermine a present atrial rate at step S1 and, if an appropriate tableentry for that atrial rate exists as determined at step S2, vary the AVDinterval by setting the AVD interval to an optimum value stored in atable which is associated with the present atrial rate at step S3. Thecontroller may be further programmed to vary the AVD interval if thereis no associated atrial rate in the table corresponding to the presentatrial rate by interpolating between two optimum AVD values stored inthe table which have associated atrial rates above and below the presentatrial rate. If an appropriate table entry for the present atrial ratedoes not exist as determined at step S2, the controller is furtherprogrammed to initialize or update the table by taking an intrinsicconduction measurement at step S4, where the intrinsic conductionmeasurement may be either an RA-LA interval or an intrinsic AV interval.If the latter is used, collection of that parameter requires a temporarycessation of pacing therapy so that intrinsically conducted ventricularbeats can occur. An optimal value for the AVD interval as a linearfunction of the intrinsic conduction measurement is then computed atstep S5, and the computed optimal value and an associated atrial ratecorresponding to the present atrial rate are stored in the table at stepS6.

Although the invention has been described in conjunction with theforegoing specific embodiments, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Other such alternatives, variations, and modifications are intended tofall within the scope of the following appended claims.

What is claimed is:
 1. A cardiac rhythm management system, comprising: aplurality of sense amplifiers configured to sense cardiac electricalactivity; a plurality of pulse generators configured to deliver pacingpulses; and a controller for controlling delivery of the pacing pulses,the controller programmed to: control delivery of ventricular pacingpulses of the pacing pulses using a programmable atrio-ventricular delay(AVD) interval in accordance with an atrial tracking oratrio-ventricular (AV) sequential pacing mode; determine a presentatrial rate; determine whether an optimum value of the AVD intervalassociated with the present atrial rate exists in a table; and set theAVD interval to the optimum value if the optimum value exists in thetable.
 2. The system of claim 1, wherein the controller is furtherprogrammed to interpolate between two optimum AVD values in the table ifthe optimum value does not exist in the table, the two optimum AVDvalues being optimum values of the AVD interval associated atrial ratesabove and below the present atrial rate.
 3. The system of claim 1,wherein the controller is further programmed to compute the optimumvalue if the optimum value does not exist in the table; and initializeor update the table using the computed optimum value.
 4. The system ofclaim 3, wherein the controller is programmed to measure an intrinsicconduction parameter; and compute the optimal value as a linear functionof the measured intrinsic conduction parameter.
 5. The system of claim4, wherein the controller is programmed to measure an interval between aright atrial sense or pace and a left atrial sense as the intrinsicconduction parameter.
 6. The system of claim 4, wherein the controlleris programmed to measure an intrinsic AV interval between an atrialsense or pace and a ventricular sense as the intrinsic conductionparameter.
 7. The system of claim 6, wherein the controller isprogrammed to measure a parameter reflective of an interventricularconduction delay, and the controller is programmed to compute an optimalvalue for the AVD interval as a linear function of the measuredintrinsic AV interval and the parameter reflective of theinterventricular conduction delay.
 8. The system of claim 7, wherein thecontroller is programmed to measure an interval between right and leftventricular senses as the parameter reflective of an interventricularconduction delay.
 9. The system of claim 1, comprising an implantabledevice including the plurality of sense amplifiers, the plurality ofpulse generators, and the controller.
 10. The system of claim 9, whereinthe implantable device is configured to deliver a cardiacresynchronization therapy.
 11. A method for operating an implantablecardiac rhythm management device, comprising: sensing cardiac electricalactivity using the implantable cardiac rhythm management device;delivering pacing pulses from the implantable cardiac rhythm managementdevice; controlling delivery of ventricular pacing pulses of the pacingpulses using a programmable atrio-ventricular delay (AVD) interval inaccordance with an atrial tracking or atrio-ventricular (AV) sequentialpacing mode; determining a present atrial rate; determining whether anoptimum value of the AVD interval associated with the present atrialrate exists in a table; and setting the AVD interval to the optimumvalue if the optimum value exists in the table.
 12. The method of claim11, further comprising interpolating between two optimum AVD values inthe table if the optimum value does not exist in the table, the twooptimum AVD values being optimum values of the AVD interval associatedatrial rates above and below the present atrial rate.
 13. The method ofclaim 11, further comprising: computing the optimum value if the optimumvalue does not exist in the table; and initialize or update the tableusing the computed optimum value.
 14. The method of claim 13, whereincomputing the optimum value comprises: measuring an intrinsic conductionparameter; and computing the optimal value as a linear function of themeasured intrinsic conduction parameter.
 15. The method of claim 14,wherein measuring the intrinsic conduction parameter comprises measuringa first interval between a right atrial sense or pace and a left atrialsense.
 16. The method of claim 14, wherein measuring the intrinsicconduction parameter comprises measuring a first interval between anatrial sense or pace and a ventricular sense.
 17. The method of claim16, wherein measuring the at least one intrinsic conduction parametercomprises measuring a second interval between right and left ventricularsenses, and computing the optimal value for the AVD interval comprisescomputing an optimal value for the AVD interval as a linear function ofthe measured first and second intervals.
 18. The method of claim 11,comprising deriving coefficients for the linear function from a linearregression analysis of clinical population data relating differentvalues of the intrinsic conduction parameter to an optimum AVD intervalfor delivering cardiac resynchronization therapy as determined bymeasurement of a cardiac function parameter.
 19. The method of claim 18,comprising indicating the optimum AVD interval for delivering cardiacresynchronization therapy by a maximum value of the cardiac functionparameter.
 20. The method of claim 19, comprising measuring a leftventricular pressure change, an arterial pulse pressure, or a cardiacoutput as the cardiac function parameter.